Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a risk factor for renal impairment. While treatment of hypertension provides significant renal protection, there is still an unmet need requiring further exploration of additional pathogenetic mechanisms. We have found that the hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is involved in renal repair. HCaRG is a small intracellular protein of 225 amino acids and its gene expression is negatively regulated by extracellular calcium concentrations. HCaRG is mostly expressed in the kidneys, with higher levels found in the spontaneously hypertensive rat than in normotensive rats. In an acute kidney injury model, HCaRG expression decreases immediately after injury but increases above baseline during the repair phase. In cell cultures, HCaRG has been shown to facilitate differentiation and to inhibit cell proliferation via p21 transactivation through the p53-independent signaling pathway. Induction of p21 independently of p53 is also observed in transgenic mice overexpressing HCaRG during the repair phase after ischemia/reperfusion injury, resulting in their improved renal function and survival with rapid re-differentiation of proximal tubular epithelial cells. In addition, transgenic mice recover rapidly from the inflammatory burst most likely as a result of maintenance of the tubular epithelial barrier. Recent studies indicate that facilitating re-differentiation and cell cycle regulation in injured renal proximal tubules might be important functions of HCaRG. We have proposed that HCaRG is a component of differential genetic susceptibility to renal impairment in response to hypertension.
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PMID:Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) and kidney diseases: HCaRG accelerates tubular repair. 2451 17

COMMD protein family is an evolutionarily conserved gene family implicated in a number of critical processes including inflammation, copper homeostasis, sodium balance, endosomal sorting and cancer. In an effort to profile the expression pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines, we found that compared with that in human bronchial epithelial (HBE) cells, the mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5, COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up-regulated in NSCLC cell lines. Here we reported that the expression of COMMD9 protein was significantly increased in various NSCLC cell lines and tissue samples. SiRNA-induced knocking down of COMMD9 inhibited proliferation and migration, arrested cell cycle at G1/S transition and induced autophagy in NSCLC cells. Mechanistically, COMMD9 interacted with the TFDP1 through COMM domain, and DNA-binding domain of TFDP1 was required for this interaction. Moreover, decreased expression COMMD9 attenuated TFDP1/E2F1 activation accompanied with enhanced p53 signaling pathway. Taken together, these findings demonstrate that COMMD9 participates in TFDP1/E2F1 activation and plays a critical role in non-small cell lung cancer.
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PMID:COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer. 2787 36